Severe gut mucosal injury induces profound systemic inflammation and spleen-associated lymphoid organ response.
Severe gut mucosal injury induces profound systemic inflammation and spleen-associated lymphoid organ response.
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DOI：
10.3389/fimmu.2023.1340442
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
临床证据表明肠道损伤、感染、炎症和全身炎症易感性增加之间存在联系。然而，用于复制这种进展的动物模型是不够的，基本机制在很大程度上仍然未知。本研究采用葡聚糖硫酸钠（DSS）诱导的结肠粘膜损伤小鼠模型，探讨肠道损伤与全身炎症的关系。用4%DSS饮用水连续处理成年小鼠在第7天产生了显著的死亡率，同时加剧了肠道损伤和可检测到的外周炎症。此外，用16S rRNA探针进行的RNAscope原位杂交观察到，在用DSS处理7天后，细菌渗透到小鼠的更深的结肠隔室中。组织学分析显示DSS治疗小鼠的肝脏和肺组织中存在炎症。此外，我们发现DSS处理的小鼠表现出外周血中丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）的升高以及肝脏中促炎细胞因子水平的升高。值得注意的是，DSS处理的小鼠表现出代谢特征减弱，CD45标记物表达减少，淋巴器官如脾脏内细胞凋亡增加。这些结果表明，高剂量DSS诱导的肠道损伤引起脓毒症样全身性炎症，其特征在于多器官损伤和严重的脾细胞凋亡以及脾中CD45+细胞的功能障碍，表明脾在肠源性全身性炎症的发病机制中的作用。总之，严重的结肠粘膜损伤模型有助于研究肠道损伤和相关的外周免疫反应，为研究与临床相关的肠道源性全身性炎症相关的机制提供了重要的框架。
Clinical evidence indicates a connection between gut injuries, infections, inflammation, and an increased susceptibility to systemic inflammation. Nevertheless, the animal models designed to replicate this progression are inadequate, and the fundamental mechanisms are still largely unknown. This research explores the relationship between gut injuries and systemic inflammation using a Dextran Sulfate Sodium (DSS)-induced colonic mucosal injury mouse model. Continuous treatment of adult mice with 4% DSS drinking water yielded a remarkable mortality rate by day 7, alongside intensified gut injury and detectable peripheral inflammation. Moreover, RNAscope in situ hybridization with 16S rRNA probe noted bacterial penetration into deeper colon compartments of the mice following treatment with DSS for 7 days. Histological analysis revealed inflammation in the liver and lung tissues of DSS-treated mice. In addition, we found that DSS-treated mice exhibited elevation of Alanine transaminase (ALT) and Aspartate transaminase (AST) in peripheral blood and pro-inflammatory cytokine levels in the liver. Notably, the DSS-treated mice displayed a dampened metabolic profile, reduced CD45 marker expression, and an increase in apoptosis within the lymphoid organ such as spleen. These findings suggest that high-dose DSS-induced gut injury gives rise to sepsis-like systemic inflammation characterized by multiple organ injury and profound splenocyte apoptosis and dysfunction of CD45+ cells in the spleen, indicating the role of the spleen in the pathogenesis of gut-derived systemic inflammation. Together, the severe colonic mucosal injury model facilitates research into gut damage and associated peripheral immune responses, providing a vital framework for investigating mechanisms related to clinically relevant, gut-derived systemic inflammation.
糖酵解和脂质氧化代谢程序对于脓毒症小鼠中新鲜分离的调节性 T 细胞至关重要。
影响因子：
3.9
作者：
通讯作者：
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影响因子：
5.6
作者：
Kaewduangduen W;Visitchanakun P;Saisorn W;Phawadee A;Manonitnantawat C;Chutimaskul C;Susantitaphong P;Ritprajak P;Somboonna N;Cheibchalard T;Wannigama DL;Kueanjinda P;Leelahavanichkul A
通讯作者：
Leelahavanichkul A